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Study of mAb 216 With Chemotherapy for Treatment of Pediatric Relapsed or Refractory B-progenitor Acute Lymphoblastic Leukemia

Phase 1
Terminated
Conditions
Leukemia, Lymphocytic, Acute
Leukemia
Acute Lymphoid Leukemia (ALL)
Interventions
Drug: Human mAb 216
Registration Number
NCT00313053
Lead Sponsor
Clare Twist
Brief Summary

This is a phase I trial in patients with relapsed or refractory leukemia of a human monoclonal antibody that kills B cell acute lymphoblastic leukemia. The trial will study the safety, pharmacokinetics, and anti-tumor activity of the antibody given as a single agent and with vincristine.

Detailed Description

Not available

Recruitment & Eligibility

Status
TERMINATED
Sex
All
Target Recruitment
4
Inclusion Criteria
  • Patients must be > than 12 months at the time of study entry.
  • Patients must have had histologic verification of B-lineage ALL with bone marrow relapse or refractory disease that is unresponsive to traditional chemotherapy.

  • For patients WITHOUT prior allogeneic bone marrow transplant (BMT):

    • Second or subsequent bone marrow relapse
    • Primary refractory marrow disease
    • M3 marrow (> 25% blasts)
  • For patients WITH prior allogeneic BMT:

    • First or subsequent bone marrow relapse post-BMT
    • M3 marrow or M2 (> 5% and < 25% blasts) if cytogenetic or variable number tandem repeat (VNTR) confirmation
  • Confirmation of antibody reactivity

  • Patient's leukemic blasts (peripheral blood or marrow) must be documented to bind mAb 216 in vitro (Teng lab).

  • Patient's red blood cell (RBC) documented to NOT express fetal "i" antigen and RBC shown to NOT bind mAb 216 in vitro (Teng lab)

  • Patient must not be eligible for therapies of higher priority

  • Performance level Karnofsky 50% for patients > 10 years of age and Lansky >= 50 for patients <= 10 years of age.

  • Life expectancy must be at least 8 weeks.

  • Patients must have fully recovered from the acute toxic effects of all prior chemotherapy, immunotherapy, or radiotherapy prior to entering this study:

    • Myelosuppressive chemotherapy: must not have been received within 2 weeks of entry onto this study.
    • Biologic: at least 7 days since the completion of therapy with a biologic agent.
  • No hematologic criteria for white blood cell (WBC), hemoglobin (Hgb), or platelets

  • Patients with thrombocytopenia should be responsive to platelet transfusions and must not have uncontrolled bleeding.

  • Adequate renal function defined as: a serum creatinine that is less than or equal to 1.5 x normal for age

  • Adequate liver function defined as: total bilirubin <= 1.5 x upper limit of normal (ULN) for age, and SGPT (ALT) <= 5 x upper limit of normal (ULN) for age

  • Adequate cardiac function defined as: shortening fraction of >= 27% by echocardiogram, or ejection fraction of >= 50% by gated radionuclide study.

  • All patients and/or their parents or legal guardians must sign a written informed consent/assent.

  • All Institutional Review Board (IRB) and Food and Drug Administration (FDA) requirements for human studies must be met.

Exclusion Criteria
  • Central nervous system (CNS) 3 or refractory CNS leukemia
  • Isolated extramedullary relapse
  • Uncontrolled infection
  • Lack of mAb 216 binding to patient's leukemic blasts in vitro
  • Binding of mAb 216 to the"i" antigen on patient's erythrocytes
  • Prior treatment with rituximab

Study & Design

Study Type
INTERVENTIONAL
Study Design
SINGLE_GROUP
Arm && Interventions
GroupInterventionDescription
Human mAb 216Human mAb 216-
Human mAb 216Vincristine-
Primary Outcome Measures
NameTimeMethod
Maximum tolerable dose without toxicity
Safety
Secondary Outcome Measures
NameTimeMethod
Decrease in leukemic blasts

Trial Locations

Locations (1)

Stanford University School of Medicine

🇺🇸

Stanford, California, United States

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